Tooth eruption is a complex and poorly understood biological process. Previous studies have suggested that it is a precisely timed, localized metabolic event in alveolar bone for which bone resorption and bone formation are required. We propose to study the relationships between tooth eruption and bone resorption using two mutations that inherit osteopetrosis, a metabolic bone disease characterized by reduced bone resorption and failure of tooth eruption. The cause(s) of reduced bone resorption will be explored in experiments designed to test the competence of osteoclast stem cells, to measure bone matrix proteins and to examine microenvironmental influences on cell development, including that of osteoclasts, in each mutation. Each of these mutations is resistant to cure by a single transplant of bone marrow from a normal littermate. Data derived from these studies will then be used to develop ways to restore bone resorption and the effects of restoration of bone resorption at birth on subsequent tooth eruption will be noted. This study is expected to provide new information about the development and control of osteoclasts and the role of these cells and their microenvironment in the development and maintenance of the dentition.